Everything You Know about Cholesterol Is Probably Wrong

Recent research suggests that cutting down on sugar does more to protect the heart than avoiding saturated fats. (Alex/Flickr)

Most of us know that too much cholesterol promotes heart disease. And many know that cholesterol comes in good and bad forms. “Bad” (low-density lipoprotein, or LDL) cholesterol clogs the arteries that pump blood to the heart and feed the brain, raising the risk of heart attack and stroke. “Good” (high-density lipoprotein, or HDL) cholesterol removes excess cholesterol and fat from the bloodstream, keeping arteries healthy.

But a little knowledge can be a dangerous thing: this good versus bad scenario offers a simplistic view of cholesterol’s role in heart disease.

Doctors assess cardiac health with routine blood tests that estimate LDL and HDL cholesterol levels along with total cholesterol and triglycerides. But cholesterol is just one component of the lipoprotein particles (spherical balls made of proteins and other lipids) that transport the water-phobic molecules through the blood. Most blood tests reflect how much cholesterol the particles carry but don’t provide any information about the particles themselves.

“It turns the cholesterol story upside down.”

“But it all starts with the particle,” says Ronald Krauss, senior scientist and director of Atherosclerosis Research at Children’s Hospital Oakland Research Institute. “The LDL particles go into the artery wall and carry the cholesterol with them. So we see the cholesterol in the plaque but it’s the particle concentration and the number of particles that really determine the process.”

That’s because smaller particles are more likely to glom on to artery walls and do so more often because they circulate in the blood longer. Once they get stuck, they undergo chemical changes that make them more toxic to arteries.

So if you have mostly small LDL particles, your cholesterol levels could be normal, but you may still be at risk for heart disease, Krauss says. “It turns the cholesterol story upside down.”

New methods for evaluating risk

That’s why more researchers are turning to methods that can measure the size and density of lipoprotein particles to better understand how heart disease develops. In a new study, published in the Journal of Lipid Research last month, researchers at the University of Pittsburgh used a method (called nuclear magnetic resonance spectroscopy) designed to measure the characteristics of lipoprotein particles as a first step to understanding how menopause may facilitate cardiovascular disease in women.

Risk of heart disease increases with age as decades of inactivity and unhealthy eating habits promote plaque formation inside artery walls, ultimately blocking blood flow and causing a heart attack. Estrogen has a beneficial effect on arteries, which helps explain why women have a lower risk of heart disease than men—until they stop menstruating.

Athlerosclerosis, the buildup of cholesterol-laden yellowish plaque inside artery walls, restricts blood flow and can lead to cardiac arrest. (Blausen/Wikipedia)

Why that edge disappears around menopause isn’t entirely clear. Lower estrogen levels may alter cholesterol abundance or metabolism, as suggested by studies linking menopause to higher levels of total cholesterol, LDL cholesterol and triglycerides. In the new study, the researchers found an association between lower levels of estrogen and “low quality” cholesterol carriers, including the smaller LDL particles associated with increased risk.

The study was small—it examined just 120 women of the 3,302 women enrolled in an ongoing study of menopausal change (the Study of Women’s Health Across the Nation). But it lends support to the notion that as women approach midlife, their falling estrogen levels may help drive a shift from high-quality lipoproteins, which can clear excess cholesterol from the bloodstream, to lower-quality molecules that can’t.

That doesn’t mean boosting estrogen is a good idea. The U.S. Preventive Services Task Force recommends against using hormone replacement therapy to reduce cardiac risk. Instead, women over 45 should get their cholesterol levels checked every five years. Routine blood tests will spot signs of trouble in most people, Krauss says, though more physicians are using the specialized tests for both women and men with diabetes, obesity or a family history of early heart disease to better assess their health status.

These numbers are particularly troubling because heart disease is largely preventable. And though people can reduce their risk—primarily by exercising, losing weight and not smoking—many don’t. Cleveland Clinic researchers reported in February that a third of adults wouldn’t change their exercise or eating habits and just half of respondents said they’d stop smoking, despite a two- to fourfold increased risk.

Though logic suggests that raising good cholesterol through drugs or supplements could help those not inclined to change bad habits, the evidence suggests otherwise. There’s no doubt that HDL has protective features, Krauss says, but there’s no guarantee that raising HDL levels will reduce your risk of heart disease. The evidence that small LDL particles promote heart disease, however, is “rock solid.”

The best way to thwart those LDL particles, Krauss says, is not by avoiding saturated fats, as we’ve long assumed. Saturated fats don’t affect the LDL particles, but sugar and carbohydrates do. “Taking away eggs and milk has virtually no effect on the bad guys,” says Krauss. “But you can make a really big improvement if you cut the sugar out.”

Liza Gross, a freelance science writer and senior editor at the biomedical journal PLOS Biology, channeled an early love of wildlife into a lifelong exploration of the numerous ways diverse species, including humans, interact in the natural world. She writes mostly about wildlife, conservation, and environmental health. Her stories reflect a deep curiosity about natural and social interactions and often highlight evolutionary relationships that remind humans of their place in, and responsibility to conserve, nature. Her article "Don't Jump!" published in Slate, won an ASJA award in the op-ed category. She's a visiting scholar at NYU, a 2013 recipient of NYU Reporting Award funding and a Dennis Hunt health journalism fellow.
Read her previous contributions to QUEST, a project dedicated to exploring the Science of Sustainability.

Anil Kumar

This is amazing info. Thank You!! I’m not sure if many people are aware of this including Physicians. Yes, there is too much sugar in our food per se (especially processed foods) and yet the Industry keeps promoting this low fat (and high carb = high sugar) myth!!

jonathanwr

The entire theory of lipids and CHD is wrong. Cholesterol does not exist in the human body to cause heart disease. It is a building block for hormones, neurotransmitters, and may even have a role in combatting infections. Statins may lower CHD risk in some people, but whether that’s due to lipid lowering effects or something else (ie mild blood thinning) isn’t clear. Moreover, other lipid lowering interventions such as niacin and estrogen do work……to lower lipids!, but both raise stroke risk and the latter heart attacks and venous blood clots. Which brings up another point – menopause doesn’t cause heart disease and estrogen doesn’t prevent it. Women have heart attacks, on average, a good 25 years after they become menopausal. The small change in the lipid profile that occurs once estrogen levels drop is insufficient to explain late life heart disease, especially in lieu of other age-related changes such as weight gain and decreasing physical activity levels.

Dr.S

The studies that showed increased risk of strokes, clots and heart attacks with “hormone replacement therapy” was mostly due to provera (in Prempro), well known for causing clots and the the other problems. The other, less discussed arm in the study went to completion (premarin only) because it didn’t have those risks.
Unfortunately, reporters aren’t doctors or pharmacists and can’t tell the difference between provera (the hazardous one), progesterone (which actually lowers those risks), premarin (horse estrogens which mostly don’t naturally occur in humans), and human-native estrogens like estradiol. So, reporting just lumps it all into “hormones” and paints them all with the “danger” brush. Even doctors aren’t great at it, often referring to Provera as progesterone, when it isn’t (as generic term for it would be a progestagen).
BTW, I used quotes in the first sentence because it should not be called replacement if you’re putting in hormones or hormone-like chemicals that weren’t there in the first place. Replacement is only if you replace what used to be there before.

jonathanwr

Sorry, that’s not entirely correct. The Premarin arm was also stopped early due to increased risk of stroke, blood clots and dementia. PremPRO increased breast cancer risk; Premarin did not.

I do agree that progesterone and progestins have hugely different effects. While neither is implicated in clotting, progesterone does not increase breast cancer risk, and it effectively reduces menopausal symptoms, helps with sleep and breathing problems, lowers blood pressure, and also will likely be the next boon for treating traumatic brain injury. Provera only helps with hot flashes.

As for Premarin vs estradiol, the latter is probably WORSE when it comes to breast cancer. Premarin (a comparatively weak estrogen in human physiology) reduced breast cancer in WHI whereas estradiol ( a woman’s own or in “replacement” form) is a far more potent stimulator of cell growth in the breast. All the drugs used to treat breast cancer either block the effects of a woman’s own estradiol or lower the body’s production of it. The good news is that sufficient progesterone can blunt estradiol’s growth promoting effects. If it works in the uterus, the same *should* hold true for the breast.

pawpaw

My students keep detailed food diaries, then analyze their habits. A significant number are eating 70-80% of their calories as carbs, primarily processed. When probed why, they describe a learned fear of eggs and dairy; that cholesterol and sat fat are the primary drivers of heart disease. And they wonder aloud of family members who lived into their 90s on breakfasts of eggs, bacon and milk, despite the nagging of family members to ‘eat healthier’.

Tony R.

The best way to get serum cholesterol down is to greatly increase vitamin C intake. The U.S. RDA of 60 mg for an adult is barely enough to prevent scurvy, but far too little to prevent chronic cardiovascular disease and strokes. Consider increasing daily intake to at least 3,000 mg, taken as two doses of 1,500 mg, morning and evening. The body consumes vitamin C to metabolize sugar, so reducing intake of sweets helps conserve the body’s supply of vitamin C.

These principles have been known for decades, but have been ignored by the pharmaceutical industry and medical establishment, because they can’t get a patent on vitamins, and people in good health don’t need to see doctors as often.